Crystal structure and Hirshfeld surface analysis of (E)-3-benzylidene-4-oxopentanoic acid

The asymmetric unit contains two independent molecules having opposite conformations and each forming self-dimers through complementary O—H⋯O hydrogen bonds. These dimers are linked by weak C—H⋯π interactions involving the phenyl ring and the olefinic double bond into zigzag chains extending along the c-axis direction. The chains are linked by C—H⋯O hydrogen bonds to form the full three-dimensional structure in which one can discern layers parallel to the bc plane.


Chemical context
Levulinic acid has various derivatives, some of which have a wide range of pharmacological activities. Photodynamic therapy in gastroenterology (Mordon et al., 2005) and cancer treatment for the detection of tumor tissue (Manzo, 2012) are some of the pharmacological applications. These derivatives are also the main compounds used in the synthesis of some pyridazinone derivatives (Boukharsa et al., 2016a,b;Zaoui et al., 2019Zaoui et al., , 2021. In our research, great attention has been given to the development of diversely functionalized heterocycles (Guerrab et al., 2020Abad et al. 2021;Missioui et al., 2021Missioui et al., , 2022a. Given the wide range of therapeutic applications for such compounds, and in continuation of our research efforts, we report the synthesis, molecular and crystal structure and a Hirshfeld surface analysis of the title compound (see Scheme).

Figure 1
The asymmetric unit of the title compound showing the atom-labelling scheme and 50% probability displacement ellipsoids. The C-HÁ Á Á interaction is depicted by a dashed line.

Figure 4
Packing viewed along the c-axis direction with O-HÁ Á ÁO and C-HÁ Á ÁO hydrogen bonds depicted, respectively, by red and black dashed lines. The C-HÁ Á Á interactions are depicted by green dashed lines and noninteracting H atoms have been omitted for clarity.

Figure 2
Overlay of the two independent molecules as found (left) and with the second one inverted (right).
see Table 1 and Fig. 3]. The unit shown in Fig. 3 is linked to others through weak C19-H19Á Á ÁO6 hydrogen bonds (Table 1) to form a three-dimensional network structure. Although these intermolecular interactions propagate in three dimensions, one can discern layers constructed by the hydrogen-bond interactions which are connected by the C-HÁ Á Á interactions. These layers are parallel to the bc plane ( Fig. 4).

Database survey
A search of the Cambridge Structural Database updated to November 2021 (Groom et al., 2016) with a search fragment consisting of the title molecule with H2A and H7, as well as all H atoms on the phenyl ring deleted, found mainly bicyclic molecules not closely related to the title molecule. Using the above search fragment but with H7 now present, one hit, namely, 3-(4-methylbenzylidene)-4-oxopentanoic acid (CSD refcode UCOXOC; Boukharsa et al., 2016a,b) was obtained (also found in the previous search). This structure also contains two independent molecules (A and B) which form A-A and B-B hydrogen-bonded inversion dimers, as seen in the present structure. The packing in UCOXOC appears to generate also a layer structure, but no mention is made of additional intermolecular interactions.

Hirshfeld surface analysis
The

Synthesis and crystallization
A mixture of benzaldehyde (0.01 mol) and levulinic acid (0.02 mol) in a solution of acetic acid (50 ml) was saturated with dry hydrogen chloride gas for 2 h. The mixture was stirred at room temperature for 24 h. The resulting product was extracted and washed with chloroform. The crude compound was crystallized from acetone to give small colourless crystals (yield: 59%; m.p 398-400 K   program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018 (Sheldrick, 2015b); molecular graphics: DIAMOND (Brandenburg & Putz, 2012); software used to prepare material for publication: SHELXTL (Bruker, 2021).

Special details
Experimental. The diffraction data were obtained from 13 sets of frames, each of width 0.5° in ω or φ, collected with scan parameters determined by the "strategy" routine in APEX3. The scan time varied between 4 and 10 sec/frame, increasing with increasing θ. Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > 2sigma(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger. H-atoms attached to carbon were placed in calculated positions (C-H = 0.95 -0.99 Å) and included as riding contributions with isotropic displacement parameters 1.2 -1.5 times those of the attached atoms. Those attached to oxygen were placed in locations derived from a difference map and refined with a DFIX 0.84 0.01 instruction.